The purpose of this project is to localize a region containing susceptibility gene that increases risk of type 1 diabetes (T1D). In a previous study, an 8 cM region at chromosome 10q25.1 showed evidence of linkage with T1D in a Bedouin Arab extended family, or tribe. A 1-2 cM region is of particular interest since three genetic markers showed evidence of linkage disequilibrium (LD) with high-risk haplotypes observed in the Bedouin Arab family. The purpose of this proposed research is to narrow the 8 cM region using LD analyses in both the Bedouin Arab family and in a sample of multiplex families from a genetically heterogeneous, European-derived Caucasian population. Specific objectives include (1) characterizing haplotype blocks in the 8 cM region to be used for further LD analyses; (2) dating the age of alleles in key SNPs that are associated with high-risk haplotypes in the Bedouin Arab family; and (3) perform LD analyses in order to find regions in the 8 cM region that are associated with type 1 diabetes or with high-risk haplotypes. The ultimate goal of this research is to identify an allele that increases risk of type 1 diabetes, which could be useful for diagnosis and treatment of T1 D. This work could also provide an example for identifying susceptibility genes for other complex diseases.